The present invention relates to a paroxetine maleate polymorph and to pharmaceutical formulations containing it; it also relates to the use and to a process for the preparation thereof. This polymorph is crystalline and is used as stable active principle in the preparation of pharmaceutical formulations indicated for disorders deriving from dysfunction of the central nervous system.
Paroxetine maleate, corresponding chemically to the (3S-trans)-3-[(1,3-benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)piperidine acid maleate of formula 
is described, together with a process for the preparation thereof, in Example 2 of U.S. Pat. No. 4,007,196 and in the same example of the corresponding Spanish patent of introduction ES-A-504997.
It is well known that paroxetine and the pharmaceutically acceptable salts thereof have a recognized activity as agents for the treatment of disorders related with dysfunction of the central nervous system, mainly, although not only, as antidepressants.
Owing to its poor handling properties, paroxetine base, is rather unsuitable for the preparation of pharmaceutical formulations and, up to date, has only been able to be used in practice in pharmaceutical formulations, as a paroxetine salt, namely, paroxetine hydrochloride. Thus, subsequent to the above mentioned U.S. patent, priority of which dates from 1974, the present inventors are unaware of the description or public use of paroxetine maleate in pharmaceutical formulations having commercial significance. On the contrary, there are numerous published patents and patent applications propounding the pharmaceutical use of paroxetine hydrochloride, both amorphous and in the non-hydrated and semi-hydrated crystalline forms thereof, among which there may be cited as examples EP-A-0188081, EP-A-0223403, WO-A-96/24595, EP-A-0810224 and U.S. Pat. No. 5,672,612, and there are numerous academic and scientific publications on the matter.
This is due to the fact that paroxetine maleate previously described in the documents U.S. Pat. No. 4,007,196 and ES-A-504997 is prepared in a form that will, hereinafter, be called Form A, which is substantially chemically unstable, which means that it undergoes degradation with time, which is a serious problem for any pharmaceutical formulation containing it.
There still exists, therefore, the need to having access to new pharmaceutically acceptable salts of paroxetine which may conveniently be used as an alternative to the different types of hydrochlorides described.
The object of the present invention is a new crystalline polymorph of paroxetine maleate, hereinafter called Form B, characterized in that it shows, substantially, the X-ray diffraction data given below in Table 1.
This Form B has superior stability properties; the invention also relates to a process for the preparation thereof.
Also object of the present invention are the pharmaceutical formulations containing the said new paroxetine maleate polymorph and the use of said polymorph in the manufacture of drugs against disorders related with dysfunction of the central nervous system.